Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32229 | 96910;96911;96912 | chr2:178543288;178543287;178543286 | chr2:179408015;179408014;179408013 |
| N2AB | 30588 | 91987;91988;91989 | chr2:178543288;178543287;178543286 | chr2:179408015;179408014;179408013 |
| N2A | 29661 | 89206;89207;89208 | chr2:178543288;178543287;178543286 | chr2:179408015;179408014;179408013 |
| N2B | 23164 | 69715;69716;69717 | chr2:178543288;178543287;178543286 | chr2:179408015;179408014;179408013 |
| Novex-1 | 23289 | 70090;70091;70092 | chr2:178543288;178543287;178543286 | chr2:179408015;179408014;179408013 |
| Novex-2 | 23356 | 70291;70292;70293 | chr2:178543288;178543287;178543286 | chr2:179408015;179408014;179408013 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | rs770101398  |
-0.974 | 1.0 | D | 0.691 | 0.384 | 0.40146981186 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.65673E-04 |
| D/N | rs770101398 |
-0.974 | 1.0 | D | 0.691 | 0.384 | 0.40146981186 | gnomAD-4.0.0 | 1.09469E-05 | None | None | None | None | I | None | 0 | 2.23604E-05 | None | 0 | 0 | None | 0 | 0 | 1.07935E-05 | 2.31863E-05 | 1.65645E-05 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.8112 | likely_pathogenic | 0.8033 | pathogenic | -0.745 | Destabilizing | 1.0 | D | 0.753 | deleterious | N | 0.486803695 | None | None | I |
| D/C | 0.9564 | likely_pathogenic | 0.9484 | pathogenic | -0.319 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | None | None | None | None | I |
| D/E | 0.8133 | likely_pathogenic | 0.8118 | pathogenic | -0.684 | Destabilizing | 0.998 | D | 0.439 | neutral | N | 0.486612657 | None | None | I |
| D/F | 0.9666 | likely_pathogenic | 0.9686 | pathogenic | -0.401 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | I |
| D/G | 0.7598 | likely_pathogenic | 0.7382 | pathogenic | -1.116 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | N | 0.504618461 | None | None | I |
| D/H | 0.8527 | likely_pathogenic | 0.8552 | pathogenic | -0.776 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | N | 0.509453853 | None | None | I |
| D/I | 0.9497 | likely_pathogenic | 0.9518 | pathogenic | 0.247 | Stabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | I |
| D/K | 0.9494 | likely_pathogenic | 0.9607 | pathogenic | -0.523 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | I |
| D/L | 0.9109 | likely_pathogenic | 0.9162 | pathogenic | 0.247 | Stabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | I |
| D/M | 0.9766 | likely_pathogenic | 0.9742 | pathogenic | 0.792 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| D/N | 0.3547 | ambiguous | 0.2705 | benign | -0.938 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | D | 0.523042047 | None | None | I |
| D/P | 0.9603 | likely_pathogenic | 0.9647 | pathogenic | -0.059 | Destabilizing | 0.999 | D | 0.771 | deleterious | None | None | None | None | I |
| D/Q | 0.9105 | likely_pathogenic | 0.9199 | pathogenic | -0.779 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | I |
| D/R | 0.921 | likely_pathogenic | 0.9379 | pathogenic | -0.43 | Destabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | I |
| D/S | 0.5149 | ambiguous | 0.472 | ambiguous | -1.275 | Destabilizing | 1.0 | D | 0.708 | prob.delet. | None | None | None | None | I |
| D/T | 0.7475 | likely_pathogenic | 0.7308 | pathogenic | -0.959 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | I |
| D/V | 0.873 | likely_pathogenic | 0.8791 | pathogenic | -0.059 | Destabilizing | 1.0 | D | 0.756 | deleterious | N | 0.50121142 | None | None | I |
| D/W | 0.9906 | likely_pathogenic | 0.992 | pathogenic | -0.233 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | I |
| D/Y | 0.7848 | likely_pathogenic | 0.8145 | pathogenic | -0.155 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | D | 0.536712368 | None | None | I |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.